Northwestern University proposes to continue to lead a consortium of organizations, the Northwestern Cancer Prevention Consortium (NCPC), to design and conduct early phase clinical trials aimed at developing new options for the prevention of cancer. To date, NCPC trials, 19 in total, have accrued 534 patients (354 from the 2003 consortium and 175 from the 2012 consortium), targeting multiple organ sites and a variety of agents. We have tested innovative concepts, e.g., transdermal drug delivery, and utilized novel biomarkers, such as nanocytological alterations. Our proposal to renew the NCPC, under the leadership of Seema A. Khan MD includes academic partners included in the current consortium and new members who are expected to add important strengths to it (the University of Toronto and City of Hope). In the new cycle of the NCPC, we will continue to build on promising approaches based on prior or ongoing successful trials, while providing oversight, consultation, and administrative support to cancer prevention research teams. We will assist in the design of cancer prevention trials, in proposal and protocol development, and in the implementation of such trials. Our overarching goal is to continue our contributions to cancer prevention science through the development of innovative, transformative, early phase trials testing new conceptual approaches that will enable clinical advances in the prevention of cancer. Our Aims are to 1. Advance high priorities in cancer prevention, for maximum impact on cancer incidence when these are advanced into clinical use. These priorities include (i) investigate novel agents and repurposed agents that target mutations and pathways known to be important in the development of cancer, (ii) novel or established biomarkers to identify individuals most like to predict benefit from a given approach, (iii) trials that will result in unifying biological themes across different organ sites, leading to protection against more than one cancer type, (iv) test innovative dosing and delivery methods, to reduce the symptom and toxicity burden for users of cancer prevention agents. 2. Provide consultation, scientific guidance, and mentoring to consortium investigators who are proposing new trial concepts; assist consortium investigators through trial design, initiation, conduct, and analysis; and to serve as the administrative hub of the consortium. We will foster communication, collaboration, and sharing of available resources between consortium members and across consortia, to maximize impact of clinical trials testing similar interventions or in similar populations. Serve as a liaison between the consortium and the NCI DCP, by maintaining and improving an NCPC 3. Advance the science of cancer prevention, through evaluation and selection of innovative or transformative concepts that result in progress that is greater than the sum of knowledge gained from the specific goals of an individual trial. We will be guided in this process by an Advisory Committee with a diverse background in cancer prevention research.